1. Field of the Invention
The present invention is broadly concerned with methods and compositions for decreasing the intestinal absorption of cholesterol in humans and animals. More particularly, the inventive methods comprise administering by ingestion a quantity of a substituted ester or ether phosphatidylcholine compound, or a composition including one or more phosphatidylcholine compounds, with the composition having a particular C.sub.18 alkyl group profile.
2 Description of the Prior Art
Cardiovascular disease is a leading cause of death in the United States, with a rather large number of people dying of cardiovascular disease by the age of 50. Atherosclerosis, which contributes to cardiovascular disease and stroke, can begin at a very early age. People with elevated serum cholesterol levels are more likely than their counterparts with normal cholesterol levels to have coronary heart disease.
Cholesterol is used by the body for the synthesis of the steroid hormones by certain endocrine glands and of bile acids by hepatocytes. Cholesterol is only found in animals, and is an essential constituent of cell membranes. Most dietary cholesterol is found in egg yolks and animal fat. Cholesterol that is taken up by the intestine is derived directly from the diet and via the biliary route. Free cholesterol is synthesized in the liver and secreted into the intestine via bile ducts. Cholesterol from the diet and bile are absorbed from the lumen of the small intestine by the intestinal epithelial cells, esterified, and incorporated intracellularly into chylomicrons and, in minor amounts, into very low density lipoproteins (VLDL), both of which are secreted into lymphatics that ultimately join the bloodstream. The chylomicrons and VLDL deliver their triacyglycerols and some of their cholesterol to cells in muscle and adipose tissue. The cholesterol-enriched chylomicron remnants and VLDL remnants (intermediate density lipoprotiens (IDL) and low density lipoproteins (LDL)) then deliver cholesterol back to the hepatocyte. The VLDL from intestinal and liver cells can be converted to LDL by hydrolysis of their triacylglycerols by lipoprotein lipase. LDL contain three-fourths of the total plasma cholesterol.
In hypercholesterolemia, the increase in the blood cholesterol level is associated mainly with a rise in LDL concentrations. However, the specific causes of hypercholesterolemia are complicated and varied. At least one kind of hypercholesterolemia is caused by a mutation in the gene for the LDL receptor that moves cholesterol out of the blood, primarily in the liver. Much more commonly, hypercholesterolemia has been associated with high dietary cholesterol, resulting in high cholesterol uptake from the intestine into the circulating blood. Reduction of hypercholesterolemia results in a delayed onset of atherosclerosis and a decrease in progression of atherosclerosis, thus reducing the risk of coronary heart disease. Specifically, there is evidence that relatively complicated plaques induced by hyperlipidemia will regress, and that further progression of atherosclerosis will cease when hyperlipidemia is removed. Therefore, efforts to prevent atherogenesis, to interrupt progression, and to promote regression of existing lesions by risk factor reduction are warranted.
Some forms of hyperlipidemia, including hypercholesterolemia, are potentially partially reversible with current techniques of preventive management. However, none of the current techniques is completely successful and many involve unwanted side effects and complications. Taking cholesterol-lowering drugs can result in a reduction in serum cholesterol. However, some drugs have serious side effects, including an increase in mortality through liver complications, or less severe side effects, such as constipation (cholestyramine), skin flushes, and muscle dysfunction. Dietary therapy is usually recommended for all patients with hypercholesterolemia but is not always effective.
Accordingly, there is a need for a method and composition which are effective in lowering intestinal absorption of cholesterol and which do not possess significant side effects.